Non-thermal plasma induces immunogenic cell deathin vivoin murine CT26 colorectal tumors

Abstract

Immunogenic cell death is characterized by the emission of danger signals that facilitate activation of an adaptive immune response against dead-cell antigens. In the case of cancer therapy, tumor cells undergoing immunogenic death promote cancer-specific immunity. Identification, characterization, and optimization of stimuli that induce immunogenic cancer cell death has tremendous potential to improve the outcomes of cancer therapy. In this study, we show that non-thermal, atmospheric pressure plasma can be operated to induce immunogenic cell death in an animal model of colorectal cancer. , plasma treatment of CT26 colorectal cancer cells induced the release of classic danger signals. Treated cells were used to create a whole-cell vaccine which elicited protective immunity in the CT26 tumor mouse model. Moreover, plasma treatment of subcutaneous tumors elicited emission of danger signals and recruitment of antigen presenting cells into tumors. An increase in T cell responses targeting the colorectal cancer-specific antigen guanylyl cyclase C (GUCY2C) were also observed. This study provides the first evidence that non-thermal plasma is a inducer of immunogenic cell death and highlights its potential for clinical translation for cancer immunotherapy.

Molecular Mechanisms of the Efficacy of Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment

“…An increase of intratumoral T-cells was observed in plasma-treated melanoma [144] and pancreatic cancer exposed to plasma-condition liquid [123]. In the latter, an increase of CRT expression was observed in tumors, which was also found in a model colorectal cancer subcutaneously injected into the skin of mice [135].…”

“…Within the tumor microenvironment, they recognize tumor antigens and lyse the target cells, helping the body to fight cancer using its endogenous weapons provided by the immune system. Using direct plasma treatment or plasma-conditioned liquids, ICD has been observed in vitro in a number of tumor cell types including, for instance, pancreatic cancer, colorectal cancer, lung cancer, and malignant melanoma [99,[131][132][133][134][135][136][137][138][139][140]. Due to the extensive poly-pragmasia of plasma sources used in the field of plasma medicine, the central mechanisms underlying plasma-induced ICD have not been commonly unraveled.…”

Cold Atmospheric Plasma: A Powerful Tool for Modern Medicine

“…The DMP molecules then lead the immune system to destroy those cells. Most importantly, some studies also suggest that CAP induces ICD, and this leads to subsequent macrophage stimulation [38,158,159].…”

Modifying the Tumour Microenvironment: Challenges and Future Perspectives for Anticancer Plasma Treatments

“…The abscopal effect grants treated cells the ability to evoke a response in cells that are at distant sites from the treated region, i.e., a systemic response that involves the immune system for its effect at sites distant from the treatment site [198]. This is the case of immunogenic cell death, a mechanism observed in plasma-treated cancer cells that induces the expression or release of danger-associated molecular patterns to activate a robust adaptive immune response against tumour cells [35,[199][200][201]. In the same way, plasma has shown to suppress the growth of treated and non-treated remote melanoma tumours in mice, which could indicate the participation of the immune response upon plasma treatment [34].…”